A series of conformationally restricted analogs of [Met5] - and [Leu 5]-enkephalin will be synthesized, tested for biological activity, and studied by various physical techniques to elucidate their conformations in aqueous solution. The constraints imposed by the conformational restrictions will allow the inference of the receptor bound conformations from the solution conformations. Comparisons of conformational features within the series and correlation with receptor binding affinities and other in vivo and in vitro activities can be used to isolate the key conformational requirements for binding and/or transduction. Since it is becoming increasingly clear that multiple opiate receptors exist and since these receptors can be expected to have different conformational requirements, the information derived from the conformationally restricted analogs of this study can be used in the design of more potent and more specific analogs. The pharmacological importance of such analogs relatively devoid of undesired activities is obvious. The enkephalin analogs will be synthesized using solid phase peptide synthesis techniques and their opiate activities tested using rat brain receptor binding, guinea pig ileum, rat tail flick, and other assays. Conformational analyses will require data from 1H and 13C nuclear magnetic resonance, circular dichroism, and laser Raman studies. The solution dynamics will be probed using these same techniques to ascertain the degree of inflexibility of the analogs.